CA2947987A1 - Inhibiteurs du facteur xia - Google Patents

Inhibiteurs du facteur xia Download PDF

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Publication number
CA2947987A1
CA2947987A1 CA2947987A CA2947987A CA2947987A1 CA 2947987 A1 CA2947987 A1 CA 2947987A1 CA 2947987 A CA2947987 A CA 2947987A CA 2947987 A CA2947987 A CA 2947987A CA 2947987 A1 CA2947987 A1 CA 2947987A1
Authority
CA
Canada
Prior art keywords
mmol
halo
chloro
heteroaryl
optionally substituted
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Abandoned
Application number
CA2947987A
Other languages
English (en)
Inventor
Weiguo Liu
Scott D. Edmondson
Zhuyan Guo
Eric Mertz
Anthony K. Ogawa
Sung-Sau So
Wanying Sun
Linda L. Brockunier
Amjad Ali
Rongze Kuang
Heping Wu
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Sharp and Dohme LLC
Original Assignee
Merck Sharp and Dohme LLC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Merck Sharp and Dohme LLC filed Critical Merck Sharp and Dohme LLC
Publication of CA2947987A1 publication Critical patent/CA2947987A1/fr
Abandoned legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4192—1,2,3-Triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/89—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to the ring nitrogen atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Pain & Pain Management (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

La présente invention concerne un composé de formule (I) (La formule chimique doit être insérée ici.) et des compositions pharmaceutiques comprenant un ou plusieurs desdits composés, ainsi que sur des méthodes d'utilisation desdits composés pour le traitement ou la prévention de thromboses, d'embolismes, d'hypercoagulabilité ou de modifications fibreuses. Ces composés sont des inhibiteurs sélectifs du facteur XIa ou des inhibiteurs doubles du facteur XIa et de la kallicréine plasmatique.
CA2947987A 2014-05-28 2015-05-22 Inhibiteurs du facteur xia Abandoned CA2947987A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201462003693P 2014-05-28 2014-05-28
US62/003,693 2014-05-28
PCT/US2015/032091 WO2015183709A1 (fr) 2014-05-28 2015-05-22 Inhibiteurs du facteur xia

Publications (1)

Publication Number Publication Date
CA2947987A1 true CA2947987A1 (fr) 2015-12-03

Family

ID=54699606

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2947987A Abandoned CA2947987A1 (fr) 2014-05-28 2015-05-22 Inhibiteurs du facteur xia

Country Status (10)

Country Link
US (1) US9783530B2 (fr)
EP (1) EP3148542B1 (fr)
JP (1) JP2017517512A (fr)
KR (1) KR20170005871A (fr)
CN (1) CN106413710A (fr)
AU (1) AU2015267305A1 (fr)
CA (1) CA2947987A1 (fr)
MX (1) MX2016015484A (fr)
RU (1) RU2016150410A (fr)
WO (1) WO2015183709A1 (fr)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105228996B (zh) 2013-03-25 2017-11-28 百时美施贵宝公司 作为因子XIa抑制剂的含取代唑类的四氢异喹啉
PE20210470A1 (es) 2014-01-31 2021-03-08 Bristol Myers Squibb Co Macrociclos con grupos p2' heterociclicos como inhibidores del factor xia
NO2760821T3 (fr) 2014-01-31 2018-03-10
EP3180325B1 (fr) * 2014-07-28 2019-03-20 Merck Sharp & Dohme Corp. Inhibiteurs du facteur xia
CN107074821B (zh) 2014-09-04 2020-05-22 百时美施贵宝公司 为fxia抑制剂的二酰胺大环化合物
US9453018B2 (en) 2014-10-01 2016-09-27 Bristol-Myers Squibb Company Pyrimidinones as factor XIa inhibitors
WO2016118403A1 (fr) * 2015-01-20 2016-07-28 Merck Sharp & Dohme Corp. Inhibiteurs du factor xia
EP3383847B1 (fr) * 2015-12-02 2022-08-24 Merck Sharp & Dohme LLC Inhibiteurs du facteur xia
WO2018039094A1 (fr) 2016-08-22 2018-03-01 Merck Sharp & Dohme Corp. Dérivés de pyridine-1-oxyde et leur utilisation en tant qu'inhibiteurs du facteur xia
CN111763171B (zh) * 2019-04-02 2023-12-22 上海美悦生物科技发展有限公司 一种FXIa凝血因子抑制剂及其药物组合物、制备方法和医药用途
WO2021057818A1 (fr) * 2019-09-27 2021-04-01 深圳信立泰药业股份有限公司 Inhibiteur de fxia, son procédé de préparation et son utilisation pharmaceutique
WO2022057849A1 (fr) * 2020-09-17 2022-03-24 浙江海正药业股份有限公司 Dérivé de pipérazine, son procédé de préparation et son utilisation
US11919881B2 (en) 2021-03-18 2024-03-05 Janssen Pharmaceutica Nv Substituted pyridine N-oxide derivatives useful as a factor XIa inhibitors
US11845748B2 (en) 2021-03-18 2023-12-19 Janssen Pharmaceutica Nv Bicyclic pyridine N-oxide derivatives useful as a factor XIa inhibitors
US11814364B2 (en) 2021-03-18 2023-11-14 Janssen Pharmaceutica Nv Pyridine N-oxide derivatives useful as factor XIa inhibitors

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7429604B2 (en) * 2004-06-15 2008-09-30 Bristol Myers Squibb Company Six-membered heterocycles useful as serine protease inhibitors
MX2007013198A (es) * 2005-04-20 2008-03-24 Johnson & Johnson Moduladores de trombina de n-oxido de piridina fluorado y procedimiento para n-oxidacion de heteroarilos que contienen nitrogeno.
KR20080080173A (ko) * 2005-12-14 2008-09-02 브리스톨-마이어스 스큅 컴퍼니 세린 프로테아제 억제제로서 유용한 6-원 헤테로사이클
WO2007109459A2 (fr) 2006-03-21 2007-09-27 Janssen Pharmaceutica, Nv Pyridines et n-oxydes de pyridine en tant que modulateurs de la thrombine
KR20100037600A (ko) * 2007-06-13 2010-04-09 브리스톨-마이어스 스큅 컴퍼니 응고 인자 억제제로서의 디펩티드 유사체
WO2013009527A2 (fr) * 2011-07-08 2013-01-17 Merck Sharp & Dohme Corp. Inhibiteurs du facteur ixa
EP3180325B1 (fr) 2014-07-28 2019-03-20 Merck Sharp & Dohme Corp. Inhibiteurs du facteur xia
US10011585B2 (en) 2014-07-28 2018-07-03 Merck Sharp & Dohme Corp. Factor XIa inhibitors
WO2016015593A1 (fr) 2014-07-28 2016-02-04 Merck Sharp & Dohme Corp. Inhibiteurs du facteur xia

Also Published As

Publication number Publication date
US20170197953A1 (en) 2017-07-13
AU2015267305A1 (en) 2016-11-03
CN106413710A (zh) 2017-02-15
KR20170005871A (ko) 2017-01-16
MX2016015484A (es) 2017-03-23
RU2016150410A3 (fr) 2018-11-30
EP3148542A1 (fr) 2017-04-05
US9783530B2 (en) 2017-10-10
JP2017517512A (ja) 2017-06-29
EP3148542A4 (fr) 2018-01-03
RU2016150410A (ru) 2018-06-28
EP3148542B1 (fr) 2019-02-27
WO2015183709A1 (fr) 2015-12-03

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Legal Events

Date Code Title Description
FZDE Discontinued

Effective date: 20211123

FZDE Discontinued

Effective date: 20211123